Are we ready for personalized cancer treatments?

I'm not sure this has the potential to become the standard of care anytime soon. However the challenge is there and most likely worth a try.

What are the current limiting factors for this approach?

- Cost (but despite the fact it is so evident, I believe it is not the main one)

- Trial Design for personalized therapies; how can we prove those therapies are effective?

- Facilities, how many cancer centers are TRULY ready to accomodate routine processing and biobanking of primary cell lines or xenograft?

- What's first? Whole exome seq or In Vitro drug response?

Mol Cancer Ther. 2010 Dec 6. [Epub ahead of print]

Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer.

Villarroel MC, Rajesh Kumar NV, Garrido-Laguna I, De Jesus-Acosta A, Jones S, Maitra A, Hruban RH, Eshleman JR, Klein AP, Laheru D, Donehower RC, Hidalgo M.

1GI Oncology, The Sidney Kimmel Cancer Center at Johns Hopkins.

Abstract

Metastasis and drug resistance are the major causes of mortality in patients with pancreatic cancer. Once developed, the progression of pancreatic cancer metastasis is virtually unstoppable with current therapies. Here we report the remarkable clinical outcome of a patient with advanced, gemcitabine-resistant, pancreatic cancer who was later treated with DNA damaging agents, based on the observation of significant activity of this class of drugs against a personalized xenograft generated from the patient's surgically resected tumor. Mitomycin C treatment, selected based on its robust preclinical activity in a personalized xenograft generated from the patient's tumor, resulted in long lasting (36+ months) tumor response. Global geneomic sequencing revealed biallelic inactivation of the gene encoding PalB2 protein in this patient's cancer, the mutation is predicted to disrupt BRCA1 and BRCA2 interactions critical to DNA double strand break repair. This work suggests that inactivation of the PALB2 gene is a determinant of response to DNA damage in pancreatic cancer and a new target for personalizing cancer treatment. Integrating personalized xenografts with unbiased exomic sequencing led to customize therapy, tailored to the genetic environment of patient's tumor and identification of a new biomarker of drug response in a lethal cancer.

Rethinking the scientific method: newyorker.com

Rethinking the scientific method: newyorker.com

The Truth Wears Off - Is there something wrong with the scientific method?

Is long-term solitary confinement torture?: newyorker.com

Is long-term solitary confinement torture?: newyorker.com

The United States holds tens of thousands of inmates in long-term solitary confinement. Is this torture?

by Atul Gawande

No survival benefit for Neoadjuvant Chemotherapy Compared With Surgery Alone for Locally Advanced Cancer of the Stomach and Cardia, results from EORTC trial 40954

Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. A Randomized EORTC trial (40954) examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines. Authors found a significantly increased R0 (radical, no tumor left) resection rate in the preoperative chemotherapy group, but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including esophagogastric junction (AEG) and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).

Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study

Cetuximab plus GEMOX was well tolerated and had encouraging antitumour activity, leading to secondary resection in a third of patients. These findings warrant further study of cetuximab plus GEMOX in a large randomised trial.

FOLFIRINOX: a new standard treatment for advanced pancreatic cancer?

by Richard Kim on Lancet oncology

Pancreatic cancer is still a lethal disease because of its tendency to undergo early subclinical metastasis to the regional lymph nodes and liver. Gemcitabine has been the standard chemotherapy for metastatic pancreatic cancer for many years on the basis of a phase 3 trial showing its clinical benefit over fluorouracil;1 however, the median survival was only 5·6 months and response rate only 5%. Since then, many trials have been done with gemcitabine being the backbone of the doublet or triplet regimens to improve overall outcome in patients.

Reconnecting with family

Research Overseas, a Nature Journal editorial

• Claire Thompson

This article was originally published in the journal Nature

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I left my native Australia nearly two years ago in a flurry of paperwork and last-minute packing. I tied up as many of the loose ends of my life as I could, put my finances in order and tried to work out what I could take with me without exceeding my baggage allowance. There seemed to be just enough time for tearful goodbyes at the airport before I was on my way to Germany.

This year, I returned to Sydney for a visit, courtesy of a conference that I was attending. It was an opportunity to present my postdoctoral work — and it was my first visit home.

Only a month before my trip, I had learned that my grandmother was ill. The high price of pursuing science overseas became all too clear: it is difficult to help and look after your family when you're half a world away. Worried, I had considered booking a flight to Sydney immediately, and pushing my trip forward by a month. The decision was not easy; there is no such thing as a quick dash home when the journey involves a 22-hour flight. If I had left then, half-done experiments would have gone to waste and my colleagues and students would have been inconvenienced, because I was in the middle of teaching a course. But after a few desperate calls to my parents, I learned that all was well — my grandmother was recovering.

I was extremely glad to see all my family when I landed in Sydney for the conference. My grandmother seemed to be in much better health. But the experience made me realize: although working overseas has many career benefits and has been a fantastic experience, the distance has significant drawbacks. I must try to put my experiments aside and take that 22-hour plane ride more often.

Linfoadenectomia nei tumori dello stomaco

Il ruolo della estensione della linfoadenectomia, ovvero della asportazione dei linfonodi, nel carcinoma dello stomaco e' un problema molto dibattuto in particolare in Europa dove la maggiore morbidita' e mortalita' perioperatoria associata ad una linfoadenectomia piu' estesa (D2) aveva di fatto messo in dubbio il vantaggio di questa procedura rispetto ad una linfoadenectomia limitata (D1).

Un follow-up a 15 anni dello stesso studio olandese che aveva messo in dubbio il vantaggio della D2, ora dimostra che una linfoadenectomia piu' estesa e' vantaggiosa in termini di minore incidenza di ripresa di malattia locale e locorgionale.

In conclusione, in tumori operabili ricevere una linfoadenectomia estesa D2 con risparmio della milza e' vantaggioso. Come ridurre il rischo legato alle maggiori complicanze di questa procedura? Rivolgersi a centri oncologici di riferimento dove vengano operati un numero cospicuo di pazienti per carcinoma gastrico.

fonte

The Lancet Oncology

Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial

Ilfet Songun, Hein Putter, Elma Meershoek-Klein Kranenbarg, Mitsuru Sasako, Cornelis J H van de Velde

Immagine tratta da http://www.hopkins-gi.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Cat_ID=AF793A59-B736-42CB-9E1F-E79D2B9FC358&GDL_Disease_ID=DB2F8EAC-4421-41DD-B04E-684AFEF2AD94

Terapie Molecolari: nuove prospettive per i tumori Neuroendocrini del pancreas

Lo studio Radiant-3 presentato al 12' World Congress of Gastrointestinal Cancer da Yao e colleghi (Huston, Texas USA) ha dimostrato l'efficacia dell'Everolimus (un inibitore del pathway di mTOR) nel rallentare la progressione di malattia in pazienti con tumori pancreatici neuroendocrini in cui vi era stata progressione nei 12 mesi precedenti.


da The Lancet Oncology
http://www.thelancet.com/journals/lanonc/issue/current

Targeted therapies: pancreatic neuroendocrine tumors join the club

In the RADIANT-3 study, a randomised, placebo-controlled phase 3 trial, James Yao (Houston, TX, USA) and colleagues assessed the efficacy and safety of everolimus (an inhibitor of the mTOR pathway) plus best supportive care versus placebo plus best supportive care in 410 patients with advanced intermediate or low-grade pancreatic neuroendocrine tumours (PNET) with disease progression within the previous 12 months. Everolimus showed a significant improvement in progression-free survival—the primary endpoint—over placebo, with a median progression-free survival of 11 months for everolimus compared with 4·6 months for placebo (HR 0·35, 95% CI 0·27–0·45, p<0·0001). The Lancet Oncology reports.

http://www.thelancet.com/journals/lanonc/issue/current

Dove si curano i tumori del Pancreas

Un link a sportello cancro del Corriere della Sera, per trovare le informazioni sui centri di eccellenza per la cura dei tumori del pancreas, fegato e vie biliari. Il servizio e' curato dalla Fondazione Veronesi.

http://www.corriere.it/sportello-cancro/db/mdc/tutte/2008/mdc07.shtml.

Late fees for Pancreatic cancer

Pancreatic adenocarcinoma is a lethal disease, with a less then 3% five year survival. Our failure in treating this cancer led to the generally accepted assumption that pancreatic cancer is indeed an extremely aggressive disease. Latest studies from Yachida and colleagues (Nature, 2010) using whole genome sequencing on a well characterized series of human primary and metastatic pancreatic cancer tissues and primary cell lines, unveiled a much milder picture of pancreatic cancer, a slow growing tumor whose natural history takes about 20 years to complete. Furthermore metastasis occurs only at the very end (2,7 years before death). Interestingly all mutations found in metastases could be found in the primary tumor, suggesting that metastases heterogeneity reflects primary tumor heterogeneity. Still early diagnosis and local control are the way to go and pancreatic cancer is no exception.

Cancer as Old Foe and Goad to Science

Good Cancer literature

Cancer as Old Foe and Goad to Science from NYTimes

Perspective: Put Integrity High on Your To-Do List - Science Careers - Biotech, Pharmaceutical, Faculty, Postdoc jobs on Science Careers

Perspective: Put Integrity High on Your To-Do List - Science Careers - Biotech, Pharmaceutical, Faculty, Postdoc jobs on Science Careers